Method of controlling rice blast with N-(alkylthiophenyl)maleimides

ABSTRACT

Disclosed are N-(alkylthiophenyl)maleimide compounds useful for controlling rice blast on rice plants.

CROSS REFERENCE TO RELATED APPLICATION

This is a division of application Ser. No. 307,608 filed Nov. 17, 1972,now U.S. Pat. No. 3,853,912.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to novel N-(alkylthiophenyl)maleimide compoundsand to compositions and methods employing such compounds in the controlof rice blast.

2. Description of the Prior Art

The present invention is useful in the control and prevention ofagricultural plant diseases, particularly in the control of rice blast(Piricularia oryzae) which is the most hazardous pest in rice plant. Inorder to prevent the rice blast, organomercury compounds such as phenylmercuric acetate and phenyl mercuric iodide have been previouslyemployed.

However, organomercury compounds and organometallic compounds in generalare residual and accumulate in the soil of treated fields and in ricehulls and thus pose environmental as well as public health problems.

Other non-metallic organo compounds known in the art also sufferdisadvantages which proscribe their use as agricultural fungicides. Themost serious drawback suffered with compounds possessing fungicidalactivity is their phytotoxicity to the host rice plant at desired dosagerates employed. N-(2'-methoxyphenyl)maleimide (the synthesis of which isdescribed in Chem. Abstracts 52:9025a; see also U.S. Pat. No. 2,205,588)is an example of such a compound which, while found to be active againstrice blast by the applicant, cannot be safely employed due to its highphytotoxicity to the host rice plant.

SUMMARY OF THE INVENTION

It has now been found in accordance with the present invention thatparticular novel substituted maleimide compounds having the formula:##SPC1##

Wherein SR is in the ortho- or meta- position; and R is an alkyl groupof from 1 to 6 carbon atoms, both inclusive, and compositions containingsuch compounds are particularly effective in controlling rice blastwithout injury to the host rice plant. The present invention alsoprovides a method for combatting rice blast which comprises contactingsaid plants to be protected with a rice blast controlling amount of atleast one compound of the following formula: ##SPC2##

Wherein

--(SR)_(n) is in the ortho or meta position;

n is 0 or 1;

m is 0 or 1, with the proviso that the sum of n + m is always 1;

R is an alkyl group of from 1 to 6 carbon atoms;

And X is oxygen or sulfur.

It is very surprising that the maleimide compounds usable according tothe present invention can be safely employed without injury to the hostplant at dosage rates at which known prior art compounds are phytotoxicto the host plant. The active compounds according to the presentinvention thus constitute a valuable addition to the art.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The term "alkyl" as used herein means both straight and branched chainradicals containing from 1 to 6 carbon atoms, as illustrated by, but notlimited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl,isoamyl, hexyl or the like. Preferred species of the present inventioninclude those maleimide compounds of Formula I wherein R is alkyl of 1to 3 carbon atoms. Further preferred are the maleimide compounds whereinR is methyl. Especially preferred are the maleimide compounds wherein SRis in the ortho position.

The instant maleimide compounds of the present invention are obtained bythe process which comprises reacting maleic anhydride with analkylmercaptoaniline compound in the presence of an inert carrier suchas, for example, ethyl ether, methylene chloride or the like, to producea corresponding alkylmercaptomaleanilic acid intermediate. Theintermediate thus obtained is subsequently dehydrated by conventionalprocedures to produce the desired N-(alkylthiophenyl)maleimide. Thereaction directed to the preparation of the alkylmercaptomaleanilic acidintermediate takes place readily at a temperature of from about 20°C. tothe reflux temperature of the reaction mixture, preferably attemperatures of from about 20° to about 50°C.

The proportions of the maleic anhydride and alkylmercaptoaniline to beemployed are not critical, some of the desired intermediate being formedupon contacting these reactants in any proportions. However, thereaction consumes the maleic anhydride and alkylmercaptoaniline startingmaterials in equimolar proportions and the use of the starting materialsin about such proportions is preferred.

In carrying out the production of the desired product, the maleicanhydride and alkylmercaptoaniline are contacted together in any orderor fashion. In a convenient procedure, the alkylmercaptoaniline reactantis slowly added portionwise to a solution of maleic anhydride andcarrier medium. The temperature of the reaction mixture is thenmaintained within the reaction temperature range for a short period oftime. During the reaction period the alkylmercaptomaleanilic acidintermediate begins to precipitate in the reaction mixture. Followingthe reaction period the reaction mixture can be cooled to insure thatmost of the intermediate is precipitated.

The dehydration of the alkylmercaptomaleanilic acid is accomplished bycontacting the aforesaid intermediate with acetic anhydride and sodiumacetate in the presence of an inert carrier, such as hereinbeforementioned. The resulting reaction mixture is heated at a temperaturefrom 60°-120°C. with the production of the desired product. The desiredN-(alkylthiophenyl)maleimide product is isolated by such conventionalprocedures as diluting the dehydration mixture with water in order toprecipitate the desired product, the latter thereafter being collectedby filtration or decantation. In another representative procedure, thereaction mixture can be distilled to remove the low boiling constituentsand obtain the N-(alkylthiophenyl)maleimide product as a residue. Thisproduct can be further purified by such procedures as washing with wateror recrystallization from an organic solvent.

In carrying out the preparation of the compound of the presentinvention, it has been found to be unnecessary to isolate thealkylmercaptomaleanilic acid intermediate. This intermediate can bedehydrated in the reaction mixture in which it was originally formed bythe addition of acetic anhydride and sodium acetate to the reactionmixture following the production of the desired intermediate and heatingthe reaction mixture to a temperature of from 60° to 120°C. The desiredN-(alkylthiophenyl)maleimide product is then separated from the reactionmixture as previously described.

The invention will be further explained in detail with reference to thefollowing examples.

EXAMPLE 1

A mixture of 2-methylmercaptoaniline (11.7 grams) in 30 milliliters(ml.) of ethyl ether was added dropwise with stirring to a solution ofmaleic anhydride (8.26 grams) in 90 ml. of ethyl ether. During thecontacting of the reactants and for a period of about one hourthereafter, the reaction mixture was heated at the boiling temperatureand under reflux. Following the heating period, the reaction mixture wascooled. During the reaction the 2-methylthiomaleanilic acid productprecipitated in the reaction mixture as a crystalline solid. This solidwas removed from the reaction mixture by filtration and dried (meltingpoint 121°C.).

The 2-methylthiomaleanilic acid (8.6 grams) obtained by filtration wassuspended in a mixture of 2.0 grams of sodium acetate and 25 ml. ofacetic anhydride. The resulting mixture was heated at about 90°C. for aperiod of one-half hour on a steam bath. Following the heating period,the reaction mixture was cooled and thereafter diluted with water.During the dilution, the desired N-(2'-methylthiophenyl)maleimideproduct precipitated from the diluted reaction mixture and was removedtherefrom by filtration. The product was thereafter dried and found tomelt at a temperature of 84°-88°C.

Analysis calculated for C₁₁ H₉ NO₂ S: C, 60.2; H, 4.1; N, 6.4. Found: C,60.7; H, 4.6; N, 6.8.

In accordance with the procedures and reactants employed in Example 1above, the replacement of 2-methylmercaptoaniline with:

3-methylthioaniline;

4-methylthioaniline;

2-isopropylthioaniline;

2-n-pentylthioaniline;

3-ethylthioaniline;

3-n-butylthioaniline; and

3-n-hexylthioaniline,

yields the following compounds of the present invention:

N-(3'-methylthiophenyl)maleimide (melting at 54°C.);

N-(4'-methylthiophenyl)maleimide (melting at 104°C.);

N-(2'-isopropylthiophenyl)maleimide (molecular weight 247.2);

N-(2'-n-pentylthiophenyl)maleimide (molecular weight 275.2);

N-(3'-ethylthiophenyl)maleimide (molecular weight 233.2);

N-(3'-n-butylthiophenyl)maleimide (molecular weight 261.2); and

N-(3'-n-hexylthiophenyl)maleimide (molecular weight 289.2).

The foregoing compounds are suitable for use in the control of riceblast in the form obtained from the reaction mixture; however, thecompounds may be further purified by recrystallization or otherconventional techniques to obtain the highly purified compound ifdesired.

The reactants employed herein are known materials which are eitherreadily available or which can be prepared according to known oranalogous procedures set forth in the art. The maleimide compound ofFormula II wherein m is 1 and X is oxygen is known in the art; see Chem.Abstracts 50:3420e, wherein the synthesis of such compound is described.The compound is also generically taught in U.S. Pat. No. 2,205,588.However, there are no literature references to the use ofN-(4'-methoxyphenyl)maleimide as a rice blast control agent.

The maleimide compounds of Formulas (I) and (II) are useful asfungicidal agents in the control of rice blast. For such uses, theunmodified compound can be utilized. However, the present invention alsoembraces the use of such compounds with inert solid or liquidagriculturally acceptable carriers. Thus, for example, a compound can bedispersed on a finely divided solid and employed therein as a dust.Also, the compounds, or a solid composition comprising the compound, canbe dispersed in water, typically with the aid of a wetting agent, andthe resulting aqueous suspension employed as a spray, drench or wash. Inother procedures, the compound can be employed as a constituent oforganic liquid compositions, oil-in-water and water-in-oil emulsions, orwater dispersions, with or without the addition of wetting, dispersing,or emulsifying agents.

It is to be understood, however, that all of the compounds claimed andcompositions containing them may not be equally effective at similarconcentrations. The exact concentration of the toxic compound to beemployed in the treating compositions is not critical and may varyconsiderably provided rice plants are contacted with a rice blastcontrolling amount of the maleimide compound or compounds employed. Theconcentration of the toxicants in liquid compositions generally is fromabout 1.0 to about 50 percent by weight, although concentrations of upto about 95 weight percent are often employed. In dusts or dryformulations, the concentration of the toxicant can be from about 1.0 toabout 10 weight percent; however, concentrations up to about 95 weightpercent are often conveniently employed. In compositions to be employedas concentrates, the toxicant can be present in a concentration of from5 to about 98 weight percent.

The compounds of this invention can also be employed in admixture withone another or applied admixed with other chemicals which are used inagronomic and horticultural management and are compatible with thecompounds of this invention. Such chemicals can be, but are notrestricted to, the classes of chemicals commonly known as plantnutrients, fertilizers, insecticides and other fungicides, which are notphytotoxic to the host rice plant.

Each of the compounds of the present invention, the utility of which isnot specifically recited hereinafter, has the ability to inhibit orotherwise control rice blast when applied at dosage levels of from about150 to about 600 or more parts per million by weight.

EXAMPLE 2

Separate aqueous compositions containingN-(2'-methylthiophenyl)maleimide and N-(3'-methylthiophenyl)maleimide,are prepared by mixing 4 parts by weight of the compound, 0.08 part byweight of sorbitan trioleate (Span 85), and 0.02 part of sorbitanmonooleate polyoxyethylene derivative (Tween 80) are dispersed in 40milliliters of acetone to produce a concentrate composition in the formof a water-dispersible liquid containing one of the test compounds asthe sole active agent.

EXAMPLE 3

A portion of each of the concentrate compositions prepared in Example 2is diluted with 20% isopropanol to provide liquid compositionscontaining from 150 to 600 parts per million by weight of activecompound. Rice plant seedlings 10 to 15 days old (variety, Caloro) weresprayed with the prepared dispersions; after natural drying, the plantswere inoculated with an inoculum of rice blast spores (Piriculariaoryzae) in 10% isopropyanol. The inoculated plants were maintained underconditions conducive to germination of rice blast spore and growth for aperiod of 10 days. After the 10 day period, the plants weremicroscopically examined and the lowest amount of active ingredientshowing 90% of prevention of spore germination determined. As a resultof such operations, it was found that both of theN-(2'-methylthiophenyl)maleimide and N-(3'-methylthiophenyl)maleimidetest compounds had an LD₉₀ of 150 parts per million. No phytotoxiceffects on the host rice plants were observed at the 150 or 600 part permillion concentrations employed.

In comparative operations, separate concentrate compositions containingeach of the N-(2'-methoxyphenyl)maleimide andN-(3'-methylphenyl)maleimide art compounds were prepared as in Example 2and diluted as above to prepare treating compositions containing from150 to 600 parts per million by weight of the test compound. Theprepared compositions were employed in similar rice blast spore treatingoperations as described above. The examination following the 10 dayperiod indicated that, while the N-(2'-methoxyphenyl)maleimide compoundhad an LD₉₀ of 150 parts per million by weight and theN-(3'-methylphenyl)maleimide compound had an LD₉₀ of 600 parts permillion, both compounds were phytotoxic to the host rice plants at theindicated dosage rates.

EXAMPLE 4

The procedures and operations of Examples two and three above wererepeated using N-(4'-methoxyphenyl)maleimide andN-(4'-methylthiophenyl)maleimide as the active test compounds. As aresult of such operations, it was found that each of the test compoundswas effective in preventing 90% of rice blast spore germination at aconcentration of 150 parts per million; no phytotoxic effects on thehost rice plants were observed at such concentration.

EXAMPLE 5

Forty-five parts by weight of N-(2'-methylthiophenyl)maleimide is mixedand ground with 5 parts by weight of Triton-155 to prepare awater-dispersible concentrate composition containing 90 percent byweight of the maleimide compound.

In a further operation, 25 parts by weight ofN-(3'-methylthiophenyl)maleimide and 10 parts by weight of Triton-155and 65 parts by weight of xylene are mixed together to prepare anemulsifiable concentrate composition containing 25 percent by weight ofthe maleimide compound.

In a similar manner, 25 parts by weight ofN-(2'-methylthiophenyl)maleimide and 71 parts of fuller's earth, 2 partsof alkyl aryl sulfonate (Nacconol NR) and 2 parts of a polymerizedsodium salt of a substituted benzoid alkyl sulfonic acid (Daxad No. 27)are mechanically mixed and ground together to prepare a concentrate inthe form of a wettable powder and containing 25 percent by weight of themaleimide compound.

A mixture of 20 parts by weight N-(3'-methylthiophenyl)maleimide, 0.1part of Nacconol NR, 0.1 part Daxad No. 27, and 100 parts of water andball-milled together to prepare a water-dispersible liquid concentratecomposition containing 20 parts by weight of the maleimide compound.

The compositions thus prepared can be dispersed in water to prepareaqueous compositions which have very desirable wetting and penetratingproperties and are adapted to distribute effective amounts of thedesired maleimide compound for control of rice blast on rice plants.

All starting materials employed in the preparation of the maleimidecompounds of the present invention are known and are either readilyavailable or can be prepared according to known or analogous proceduresset forth in the prior art.

While this invention has been described and exemplified in terms of itspreferred embodiment, those skilled in the art will appreciate thatmodifications can be made without departing from the spirit and scope ofthe invention.

I claim:
 1. A composition comprising an inert agriculturally acceptablecarrier and a rice-blast controlling amount of a compound of theformula: ##SPC3##wherein SR is in the ortho- or meta- position and R ismethyl.
 2. The composition of claim 1 wherein the compound isN-(2'-methylthiophenyl)maleimide.
 3. The composition of claim 1 whereinthe compound is N-(3'-methylthiophenyl)maleimide.
 4. A method forcontrolling rice blast on a rice plant comprising applying to the plantto be protected a rice blast controlling amount of a compound having theformula: ##SPC4##wherein --(SR)_(n) is in the ortho or meta position; nis 0 or 1; m is 0 or 1, with the proviso that the sum of n + m is always1; R is an alkyl group of from 1 to 6 carbon atoms; and X is oxygen orsulfur.
 5. The method of claim 4 wherein n is
 1. 6. The method of claim4 wherein m is
 1. 7. The method of claim 4 wherein --(SR)_(n) is in theortho position.
 8. The method of claim 4 wherein the compound isN-(2'-methylthiophenyl)maleimide.
 9. The method of claim 4 wherein thecompound is N-(3'-methylthiophenyl)maleimide.
 10. The method of claim 4wherein the compound is N-(4'-methylthiophenyl)maleimide.
 11. The methodof claim 4 wherein the compound is N-(4'-methoxyphenyl)maleimide.